The research proposed is designed to advance our basic knowledge and understanding of the control of gene expression in higher organisms. A significant aim is to distinguish between conventional control mechanisms which respond primarily to environmental changes, and endogenous controls, which activate specific genetic loci at particular developmental times. Efficient techniques will be employed to isolate specific types of regulatory mutants in Neurospora. Such mutants will be studied by parallel genetic and biochemical approaches to reveal their mode of action. The biosynthesis of specific enzymes at different developmental stages and the potential regulation over enzyme activity by feedback inhibition and protein turnover will be studied to gain an overall picture of the interrelating systems which serve to regulate an entire pathway, that of sulfate assimilation and methionine biosynthesis. The process of sulfate transport, its control, and the development of functional permease systems, properly integrated into the cellular membrane will be investigated to gain an understanding of the regulation of a pathway at the level of entry of metabolites into the intracellular pool. An allied and important goal is to gain new insight into the biochemical genetics of morphogenesis. Genetic and biochemical studies are planned to reveal the biochemical basis underlying certain morphological mutants, with particular reference to the role which sulfur metabolism may play in differentiation and morphogenesis. Bibliographic references: Hanson, M.A. and G.A. Marzluf. 1975. Control of the synthesis of a single enzyme by multiple regulatory circuits in Neurospora crassa. Prof. Nat. Acad. Sci. USA 72, 1240-1244; Reinert, W.R. and G. A. Marzluf. 1975. Regulation of the purine catabolic enzymes in Neurospora crassa. Arch. Biochem. Biophys. 166, 565-574.